The epidermal growth factor receptor (EGFR) is a transmembrane protein, a receptor for members of the epidermal growth factor family (EGF family) and other extracellular protein ligands. There are four closely related members of the EGFR family: EGFR (ErbB-1), HER2/neu (ErbB-2), Her 3 (ErbB-3) and Her 4 (ErbB-4), each being a receptor tyrosine kinase. EGFR is frequently overexpressed or mutated in majority of human cancers, such as cancers of the head and neck, breast, ovary, cervix, lung etc. As an example, EGFR is overexpressed in 62% of non-small cell lung cancer cases, and its expression is correlated with a poor prognosis. Overexpression of EGFR has also been reported in up to 40% of breast cancer cases and is known to correlate with poor clinical outcome. Further, many epithelial cancer cells contain mutations on EGFR that constitutively activate EGFR at expression or activity level and are thought to promote the occurrence, progression, and/or metastasis of cancer.
Due to its frequent and significant involvement in various human malignancies, EGFR has been a major target in cancer therapy. Currently available treatment strategies targeting EGFR involve the use of EGFR tyrosine kinase inhibitors and anti-EGFR antibodies. While varying degree of efficacy has been reported, cancer patients receiving the EGFR antagonist therapy tend to develop resistance to the treatment over time, which ultimately renders such treatment ineffective. Thus, there exists an urgent need to establish new and more effective therapeutic methods for treating conditions especially cancers where overexpression of EGFR or inappropriate activation of EGFR-mediated cellular signaling is a significant component. The present invention fulfills this and other related needs.